Erytrocyte-related phenotypes and genetic susceptibility to thrombosis

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• 作者：Angel F. Remacha^a ; ^{aremacha@santpau.cat" class="auth_mail" title="E-mail the corresponding author} ; Noè ; lia Vilalta^b ; M. Pilar Sard&agrave ; ^a ; Joan Milló ; n^b ; Nuria Pujol-Moix^b ; ^d ; Andrey Ziyatdinov^c ; Jordi Fontcuberta^b ; Josep Nomdedeu^a ; José ; Manuel Soria^c ; Juan Carlos Souto^b
• 关键词：Thrombosis ; Red blood cell ; Iron ; Reticulocytes ; Heritability
• 刊名：Blood Cells, Molecules and Diseases
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：59
• 期：Complete
• 页码：44-48
• 全文大小：254 K

文摘

Venous thromboembolism (VTE) is a common disease that involves the interaction of genetic and environmental risk factors. Previous studies have estimated a heritability of approximately 60% for the risk of VTE. Using variance analysis, intermediate phenotypes related to thrombosis have been used to identify genetic risk factors. Erythrocyte intermediate phenotypes are good candidates for VTE risk factors. We investigated the relationship of erythrocyte-related phenotypes with the risk of VTE. Our study used the Genetic Analysis of Idiopathic Thrombophilia 2 (GAIT2 Project) sample, which consisted of 35 extended pedigrees (including a total of 935 individuals). The sample had 120 subjects with thromboembolism (86 with VTE, 47 with arterial thrombosis and 13 with both). The following risk factors were evaluated: Red blood cell parameters, reticulocytes, serum iron, total iron binding capacity, serum ferritin, serum transferrin receptor (STFR), and haptoglobin. Using the variance component method, heritability (h²) and the phenotypic, genetic and environmental correlations with VTE were estimated. The h² of VTE was 0.67. Most erythrocyte parameters showed significantly high h². In addition, VTE was genetically correlated with: hematocrit (ρ_G = 0.52, p = 0.01), red blood cell distribution width (RDW) (ρ_G = 0.28, p = 0.05), immature reticulocyte fraction (IRF) (ρ_G = 0.45, p = 0.008), transferrin saturation index (ρ_G = − 0.7, p = 0.05), and STFR (ρ_G = 0.4, p = 0.006). In conclusion, a genetic relationship between erythrocyte intermediate phenotypes and VTE was demonstrated. Also, we identified 5 phenotypes as risk factors. These phenotypes are useful in the search for genes that affect VTE.